Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present study was to determine whether the physiological dopamine prodrug, L-dopa, could suppress streptozotocin-induced diabetic glomerular hyperfiltration, and thus prevent further evolution of the diabetic nephropathy. Male Wistar rats treated with streptozotocin (60 mg/kg, intravenously) rapidly developed hyperglycemia which was stabilized (congruent to 4 g/L) by a daily insulin injection. Within two weeks, a significant increase in glomerular filtration rate (GFR) and a rise in the filtration fraction were observed as described in the early stage of diabetic nephropathy. Increase in both GFR and in the filtration fraction were normalized by treating the rats with L-dopa (10 mg/kg, subcutaneously, twice a day for one week). The effects of L-dopa were linked to endorenal DA synthesis and to DA-1 receptor stimulation since both carbidopa and SCH 23390 suppressed them.
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PMID:L-dopa and streptozotocin-induced diabetic nephropathy in rats. 214 90

The early renal effects associated with streptozotocin-induced diabetes in rats (glomerular hyperfiltration and increase in filtration fraction) are similar to modifications reported in the early stage of human diabetic nephropathy. We examined the reversibility of these early renal diabetic effects by dopamine, which might correct glomerular hyperfiltration thanks to its preferential vasodilatory action on glomerular efferent arterioles. A dopamine prodrug, L-dopa was used to increase endorenal dopamine synthesis. Studies were carried out on streptozotocin-treated (60 mg/kg, i.v.) Wistar rats, supplemented with NPH insulin (2 to 3 U/day) such as to stabilize hyperglycemia at 22 mmol/l. One week after diabetes induction, animals were treated during a week either with L-dopa (10 mg/kg, s.c. twice daily) or L-dopa plus a dopa-decarboxylase inhibitor, carbidopa (10 mg/kg, s.c. 30 min before each L-dopa injection) or L-dopa plus a selective D1 receptor antagonist, SCH 23390 (100 micrograms/kg, s.c., with each L-dopa injection). Control diabetic animals received the solvent of L-dopa and control non-diabetic animals received the solvent of streptozotocin. After one week of L-dopa or other treatment, the renal functions of the rats were investigated (polyfructosan and PAH clearances) under inactin anaesthesia. As expected, streptozotocin induced glomerular hyperfiltration (1.3 +/- 0.07, n = 14, versus 0.93 +/- 0.05 ml/min.g kidney weight in non-diabetic controls, p less than 0.001) and an increase in filtration fraction (52.4 +/- 5.1 versus 32.1 +/- 1.7%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Prevention by L-dopa of early renal consequences of diabetes induced by streptozocin in rats]. 214 79

Both insulin-dependent diabetes mellitus (IDDM) and unilateral nephrectomy (UNX) are associated with an increase in the glomerular filtration rate. Glomerular hyperfiltration has been linked to intraglomerular hypertension in both conditions, although it has only been linked to the development of nephropathy in diabetes. In this study, we examined the possibility of preventing diabetic nephropathy through early dopamine (DA) prodrugs treatment and we also investigated the participation of endogenous DA in the acute functional adaptation of the remaining kidney after UNX. In an animal model of IDDM (steptozotocin-treated Wistar rats), the early increase in the glomerular filtration rate was prevented by treatment with DA prodrugs (L-dopa or gludopa), an effect which was mimicked by fenoldopam (a D1 agonist) and suppressed by carbidopa and SCH 23390 (a D1 antagonist). An increase in endorenal DA synthesis and the subsequent stimulation of vascular D1 receptors appears to prevent early glomerular hyperfiltration in diabetic rats. However, in a long-term study lasting more than one year, streptozotocin-diabetic Wistar rats (unlike to diabetic Munich Wistar rats) failed to develop overt nephropathy characterized by albuminuria and systemic hypertension. During long-term treatment of diabetic rats with L-dopa, the renal availability of DA was diminished. The acute adaptation of the remaining kidney to UNX took the form of an early transient pressor effect with a moderate increase in the glomerular filtration rate and renal blood flow, and a marked decrease in tubular sodium reabsorption. SCH 23390 suppressed the hemodynamic and tubular responses to UNX, suggesting that endogenous DA plays a key role.
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PMID:Pathophysiological role of dopamine in the kidney: effects in diabetes mellitus and after contralateral nephrectomy. 852 42